Genomics of Pulmonary Arterial Hypertension: Implications for Therapy

Geraci, Mark W.; Bull, Todd; Tuder, Rubin M.

doi:10.1016/j.hfc.2009.08.001

Cited by 11 publications

(6 citation statements)

References 134 publications

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“…The causes for the increase in PVR have been thought to include vascular remodeling, endothelial dysfunction, heightened levels of endothelin-1 and the presence of a proinflammatory state. Genetic pathways have also been linked to the progression of PAH [2].…”

mentioning

confidence: 99%

Evaluating exercise capacity in patients with pulmonary arterial hypertension

Babu¹,

Myers

Arena

et al. 2013

Expert Review of Cardiovascular Therapy

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Cardiopulmonary exercise testing (CPET), performed in a clinical laboratory setting, has long been used to evaluate persons with suspected or confirmed cardiopulmonary disease. This form of testing is now recognized as the gold standard for evaluating a person's aerobic exercise performance. In addition, simplified submaximal approaches to assessing functional capacity are readily available; perhaps the most recognized being the 6-min walk test. With the growing interest in CPET for evaluating patients with pulmonary artery hypertension (PAH), gaining a better understanding of the significance of the various outcomes used and how they are relevant to evaluating patients with PAH is a an important endeavor. This review highlights the utility of CPET; the various outcomes that can be derived from this assessment and the various functional tests commonly used as well as related tests that may have a role in clinical assessment of patients with PAH.

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mentioning

confidence: 99%

Evaluating exercise capacity in patients with pulmonary arterial hypertension

Babu¹,

Myers

Arena

et al. 2013

Expert Review of Cardiovascular Therapy

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“…e inverse correlation between age and mPAP may indicate other factors contribute to the development of PAH in ASD patients. e presence of concomitant genetic background may predispose some patients to the development of PAH [28]. e pulmonary overflow due to the chronic left-to-right shunt is the triggering factor for development of PAH.…”

Section: Discussionmentioning

confidence: 99%

Profile of Endothelin-1, Nitric Oxide, and Prostacyclin Levels in Pulmonary Arterial Hypertension Related to Uncorrected Atrial Septal Defect: Results from a Single Center Study in Indonesia

Dinarti

Hartopo

Anggrahini

et al. 2020

Cardiology Research and Practice

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Background and Objectives. Pulmonary arterial hypertension (PAH) pathomechanism involves an increased plasma level of endothelin-1 and a reduced plasma level of prostacyclin and nitric oxide. Whether similar mechanisms prevail in PAH associated with atrial septal defect (ASD) is unclear. This study aimed to investigate the relationship of endothelin-1, prostacyclin, and nitric oxide with PAH in uncorrected ASD in Indonesian population. Methods. The study design was cross-sectional. The subjects were adult uncorrected secundum ASD with PAH. Pulmonary artery pressure was measured with right heart catheterization. Pulmonary venous blood was obtained during catheterization for measuring endothelin-1, prostacyclin, and nitric oxide. Correlation tests were performed to determine any association between biomarkers and mean pulmonary artery pressure (mPAP). The levels of biomarkers were compared based on the severity of PAH. Statistical significance was determined at p<0.05. Results. Forty-four subjects were enrolled in this study. Endothelin-1 level and mPAP had significant moderate positive correlation (r = 0.423 and p value = 0.004). However, no significant correlation was observed between prostacyclin, nitric oxide levels, and mPAP. The pattern of endothelin-1, prostacyclin, and nitric oxide was distinctive. Levels of endothelin-1 were incrementally increased from mild, moderate, to severe PAH. The levels of prostacyclin and nitric oxide had similar pattern in association with the severity of PAH, which was increased in mild-to-moderate PAH but decreased in severe PAH. Conclusions. There was a distinctive pattern of endothelin-1, prostacyclin, and nitric oxide based on severity of PAH in adult uncorrected ASD. Significant correlations existed between endothelin-1 and the severity of PAH and mPAP.

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“…These approaches focus on gene networks involved in cellular processes such as energy metabolism [54], cell survival and proliferation among others [7,55] known to be dysregulated in PAH. Computational methods are relatively fast to implement and accelerate target discovery; however, due to the potentially large data output, this strategy needs to be coupled with a solid bioinformatic analysis platform that can integrate compound–target associations obtained from chemical biology and pharmacological databases [56,57].…”

Section: Novel Strategies For Drug Discovery In Pahmentioning

confidence: 99%

Novel approaches to pulmonary arterial hypertension drug discovery

Sung¹,

Yuan²,

Perez³

2016

Expert Opinion on Drug Discovery

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Introduction Pulmonary arterial hypertension (PAH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. The goal of drug development for PAH is to develop effective therapies that halt, or ideally, reverse the obliterative vasculopathy that results in vessel loss and obstruction of blood flow to the lungs. Areas Covered This review summarizes the current approach to candidate discovery in PAH and discusses the currently available drug discovery methods that should be implemented to prioritize targets and obtain a comprehensive pharmacological profile of promising compounds with well-defined mechanisms. Expert opinion To improve the successful identification of leading drug candidates, it is necessary that traditional pre-clinical studies are combined with drug screening strategies that maximize the characterization of biological activity and identify relevant off-target effects that could hinder the clinical efficacy of the compound when tested in human subjects. A successful drug discovery strategy in PAH will require collaboration of clinician scientists with medicinal chemists and pharmacologists who can identify compounds with an adequate safety profile and biological activity against relevant disease mechanisms.

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Genomics of Pulmonary Arterial Hypertension: Implications for Therapy

Cited by 11 publications

References 134 publications

Evaluating exercise capacity in patients with pulmonary arterial hypertension

Evaluating exercise capacity in patients with pulmonary arterial hypertension

Profile of Endothelin-1, Nitric Oxide, and Prostacyclin Levels in Pulmonary Arterial Hypertension Related to Uncorrected Atrial Septal Defect: Results from a Single Center Study in Indonesia

Novel approaches to pulmonary arterial hypertension drug discovery

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